Reviews & Analysis

The dog is a unique model of human complex disease, and its remarkable population history makes trait mapping especially powerful. This article reviews the mapping strategies available in dogs, some key biological findings and the implications for other experimental organisms.

Sequenced genomes are accumulating rapidly, but our understanding of the functions they encode is progressing more slowly. This Review investigates the amount of functional sequence in metazoan genomes, how it has evolved and how it differs between species.

This Review discusses the role of BMP signalling in neural patterning. Comparative evo–devo analyses show that this genetic system has a conserved function in organizing the developing central nervous system and that it was probably already present in the bilaterian ancestor.

Single-strand breaks are the most common type of DNA damage that arise in cells. Keith Caldecott discusses the molecular mechanisms and organization of the pathways that repair these lesions and the link between defects in these pathways and hereditary neurodegenerative disease.

There are now 14 DNA polymerases in the human genome. This article explores the function of these molecules in replicating DNA, their regulation and involvement in disease, and how specific properties of each polymerase might be targeted for therapeutic ends.

It is well known that prokaryotes regularly exchange genes by horizontal transfer, but there is increasing evidence that such processes also have an important role in eukaryotic evolution, although the extent of this differs widely between lineages.

In contrast to growth control, gene expression responses to stress involve distinctive regulatory mechanisms that are characterized by high levels of noise. These features allow organisms to respond quickly to unpredictable environmental changes, and recent studies suggest that they also promote the evolvability of gene regulation.

Studies in the chick, mouse, zebrafish and other vertebrate model systems are beginning to uncover the complexities of skeletal muscle development. Distinct sets of precursor cells and various different gene regulatory networks are responsible for the spatial and temporal heterogeneity of the process.

It is now feasible to dissect the influence of the environment on gene function in many species — a desirable goal from a biomedical, agricultural and evolutionary perspective. This article describes the progress made so far, and the analytical challenges to be overcome.

Psychiatric genetics has been fraught with controversy owing to the irreproducibility of many claimed risk factors. There is now some cause for optimism thanks to larger sample sizes and the incorporation of intermediate traits, rare mutations and environmental risk components into the analyses.

Progress in understanding the genetic basis of susceptibility to multiple sclerosis — a debilitating and genetically complex disease — is being obtained by a combination of advances in genome studies (through genome-wide association studies) and powerful systems-level approaches.

How are the complex and varied roles of retinoic acid orchestrated at multiple developmental stages? Recent studies have highlighted the importance of tightly regulating its distribution, of switching the activities of its nuclear receptors, and of interactions with other key developmental signalling molecules.

RNAi, a common gene knockdown technique, has been widely used in a variety of genetic screens. As part of our 'art and design of genetic screens' series, the authors discuss RNAi assay design and analytical approaches for large-scale screening experiments in cells and whole-animal experiments.

Rather than being a mark of irreversible gene silencing that localizes mainly to promoters and intergenic regions, epigenomics approaches are revealing DNA methylation as a surprisingly dynamic regulator of gene expression that might also have important roles within gene bodies.

Advances in genomics and gene mapping allow sets of candidate genes to be identified for use in monitoring adaptive responses to specific environmental stresses. Such toolkits will allow us to predict the ability of species to adapt to changing environments.

Linkage disequilibrium was once a concept used little outside population genetics. However, in the genomics era it has become fundamental to our understanding of the genetic variation that is behind complex traits and evolutionary change.

Making ethanol from cellulose-containing parts of plants is a promising route to abundant biofuel production. Using genetics to decrease the need for crop pretreatment and processing, and to increase yield, will be important in making bioethanol an affordable and plentiful fuel.

The combination of environmental change and a rapidly increasing human population is putting global food supplies in danger. Crop improvements that increase yields and enable plants to withstand abiotic stresses will provide an important route to tackling this urgent problem.

Some DNA viruses express abundant non-coding RNAs, but their function has been mostly unknown. Several recent reports show how viruses can use non-coding RNAs to tackle host defences and control their gene expression levels.

The Gene Ontology project has provided a powerful tool for interpreting the biological significance of both experimental and computational data. However, some appreciation of how the database works is essential to avoid misinterpretations.